1825-P: Low-Glucose Conditions Enhance Metformin’s Antiproliferative Effect in MEC-1 Chronic Lymphocytic Leukemia Cells and Implicate miR-15a/16-1 Regulation and Protein Expression

Introduction and Objective: Diabetes and cancer share metabolic pathways and glucose availability can influence tumor cell growth. Metformin has demonstrated anticancer activity in preclinical models, potentially via energy-sensing pathways. This study evaluated whether low-glucose culture conditions enhance metformin’s effects on growth/viability and apoptosis in the MEC-1 chronic lymphocytic leukemia (CLL) cell model, with mechanistic relevance to miR-15a/16-1. Methods: MEC-1 cells were cultured in low- vs higher-glucose media (5 vs 11 mM) and treated with metformin (1, 5, 10, 20, 40 mM) for 24-48 h. Cell growth/viability was assessed microscopically. Apoptosis/necrosis were quantified by flow cytometry. The potential involvement of miR-15a/16-1 and anti-apoptotic protein regulation was considered based on current evidence in CLL biology. Results: Metformin reduced MEC-1 growth and viability more prominently under low-glucose conditions; at 20 mM metformin at 48 hours, viability decreased by 30% in low-glucose media vs 2% in higher-glucose media. Flow cytometry was consistent with microscopy, showing a higher proportion of late apoptotic cells versus control in metformin-treated conditions. Findings support a plausible role for miR-15a/16-1-linked anti-apoptotic regulation in the observed effect. Conclusion: In a MEC-1 CLL model, low-glucose conditions appear to potentiate metformin’s anti-proliferative and pro-apoptotic effects. These data support further mechanistic experiments to directly quantify miR-15a/16-1 modulation and downstream anti-apoptotic targets under metformin exposure. Disclosure E. Manthou: None. K. Psatha: None. P. Rakitzi: None. T. Koufakis: Speaker's Bureau; Current; Novo Nordisk, Lilly, Menarini Group. Advisory Panel; Current; Roche Diabetes Care. Speaker's Bureau; Current; AstraZeneca, Boehringer Ingelheim International GmbH. K. Kotsa: None. M. Aivaliotis: None.